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Heterozygous p53 knockout mouse model for dehydropyrrolizidine alkaloid-induced carcinogenesis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Brown, Ammon W. Stegelmeier, Bryan L. Colegate, Steven M. Panter, Kip E. Knoppel, Edward L. Hall, Jeffery O.
Description	Country affiliation: United States Author Affiliation: Brown AW ( USDA/ARS Poisonous Plant Research Laboratory, Logan, UT, USA.); Stegelmeier BL ( USDA/ARS Poisonous Plant Research Laboratory, Logan, UT, USA.); Colegate SM ( USDA/ARS Poisonous Plant Research Laboratory, Logan, UT, USA.); Panter KE ( USDA/ARS Poisonous Plant Research Laboratory, Logan, UT, USA.); Knoppel EL ( USDA/ARS Poisonous Plant Research Laboratory, Logan, UT, USA.); Hall JO ( Utah Veterinary Diagnostic Laboratory, Utah State University, Logan, UT, USA.)
Abstract	Dehydropyrrolizidine alkaloids (DHPA) are a large, structurally diverse group of plant-derived protoxins that are potentially carcinogenic. With worldwide significance, these alkaloids can contaminate or be naturally present in the human food supply. To develop a small animal model that may be used to compare the carcinogenic potential of the various DHPAs, male heterozygous p53 knockout mice were administered a short-term treatment of riddelliine 5, 15 or 45 mg kg(-1) bodyweight day(-1) by oral gavage for 14 days, or dosed a long-term treatment of riddelliine 1 mg kg(-1) bodyweight day(-1) in pelleted feed for 12 months. Exposure to riddelliine increased the odds of tumor development in a dose-responsive manner (odds ratio 2.05 and Wald 95% confidence limits between 1.2 and 3.4). The most common neoplastic process was hepatic hemangiosarcoma, which is consistent with published lifetime rodent riddelliine carcinogenesis studies. Angiectasis (peliosis hepatis) and other previously unreported lesions were also identified. The results of this research demonstrate the utility of the heterozygous p53 knockout mouse model for further investigation of comparative carcinogenesis of structurally and toxicologically different DHPAs and their N-oxides.
File Format	HTM / HTML
ISSN	0260437X
Issue Number	12
Volume Number	35
e-ISSN	10991263
Journal	Journal of Applied Toxicology
Language	English
Publisher	Wiley
Publisher Date	2015-12-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Hemangiosarcoma Chemically Induced Heterozygote Liver Neoplasms Pyrrolizidine Alkaloids Toxicity Tumor Suppressor Protein P53 Genetics Administration, Oral Animals Carcinogenicity Tests Dose-response Relationship, Drug Pathology Male Mice, Knockout Isolation & Purification Senecio Chemistry Journal Article
Content Type	Text
Resource Type	Article
Subject	Toxicology

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